Expandable and reversible copy number amplification drives rapid adaptation to antifungal drugs.

Abstract:

:Previously, we identified long repeat sequences that are frequently associated with genome rearrangements, including copy number variation (CNV), in many diverse isolates of the human fungal pathogen Candida albicans (Todd et al., 2019). Here, we describe the rapid acquisition of novel, high copy number CNVs during adaptation to azole antifungal drugs. Single-cell karyotype analysis indicates that these CNVs appear to arise via a dicentric chromosome intermediate and breakage-fusion-bridge cycles that are repaired using multiple distinct long inverted repeat sequences. Subsequent removal of the antifungal drug can lead to a dramatic loss of the CNV and reversion to the progenitor genotype and drug susceptibility phenotype. These findings support a novel mechanism for the rapid acquisition of antifungal drug resistance and provide genomic evidence for the heterogeneity frequently observed in clinical settings.

journal_name

Elife

journal_title

eLife

authors

Todd RT,Selmecki A

doi

10.7554/eLife.58349

subject

Has Abstract

pub_date

2020-07-20 00:00:00

issn

2050-084X

pii

58349

journal_volume

9

pub_type

杂志文章

相关文献

eLife文献大全
  • Untwisting the Caenorhabditis elegans embryo.

    abstract::The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.10070

    authors: Christensen RP,Bokinsky A,Santella A,Wu Y,Marquina-Solis J,Guo M,Kovacevic I,Kumar A,Winter PW,Tashakkori N,McCreedy E,Liu H,McAuliffe M,Mohler W,Colón-Ramos DA,Bao Z,Shroff H

    更新日期:2015-12-03 00:00:00

  • Intracellular sphingosine releases calcium from lysosomes.

    abstract::To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-dr...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.10616

    authors: Höglinger D,Haberkant P,Aguilera-Romero A,Riezman H,Porter FD,Platt FM,Galione A,Schultz C

    更新日期:2015-11-27 00:00:00

  • Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites.

    abstract::While the dynamin GTPase Drp1 plays a critical role during mitochondrial fission, mechanisms controlling its recruitment to fission sites are unclear. A current assumption is that cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Using live-cell microscopy, we find evidence for a diff...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.11553

    authors: Ji WK,Hatch AL,Merrill RA,Strack S,Higgs HN

    更新日期:2015-11-26 00:00:00

  • Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons.

    abstract::Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the localized mRNA population within and between cell types is unknown. Here we describe the unbiased transcriptomic characterization ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.63092

    authors: Perez JD,Dieck ST,Alvarez-Castelao B,Tushev G,Chan IC,Schuman EM

    更新日期:2021-01-06 00:00:00

  • Individual recognition and the 'face inversion effect' in medaka fish (Oryzias latipes).

    abstract::Individual recognition (IR) is essential for maintaining various social interactions in a group, and face recognition is one of the most specialised cognitive abilities in IR. We used both a mating preference system and an electric shock conditioning experiment to test IR ability in medaka, and found that signals near...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.24728

    authors: Wang MY,Takeuchi H

    更新日期:2017-07-11 00:00:00

  • Identification of ligand-specific G-protein coupled receptor states and prediction of downstream efficacy via data-driven modeling.

    abstract::Ligand binding stabilizes different G protein-coupled receptor states via a complex allosteric process that is not completely understood. Here, we have derived free energy landscapes describing activation of the β2 adrenergic receptor bound to ligands with different efficacy profiles using enhanced sampling molecular ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.60715

    authors: Fleetwood O,Carlsson J,Delemotte L

    更新日期:2021-01-28 00:00:00

  • AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation.

    abstract::Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.21690

    authors: Seo AY,Lau PW,Feliciano D,Sengupta P,Gros MAL,Cinquin B,Larabell CA,Lippincott-Schwartz J

    更新日期:2017-04-10 00:00:00

  • The transcription factor Pitx2 positions the embryonic axis and regulates twinning.

    abstract::Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest know...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.03743

    authors: Torlopp A,Khan MA,Oliveira NM,Lekk I,Soto-Jiménez LM,Sosinsky A,Stern CD

    更新日期:2014-12-11 00:00:00

  • Common concepts for bacterial collectives.

    abstract::The expansion of bacterial swarms and the spreading of biofilms can be described by a unified biophysical theory that involves both active and passive processes. ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.47019

    authors: Jeckel H,Matthey N,Drescher K

    更新日期:2019-04-30 00:00:00

  • mPFC spindle cycles organize sparse thalamic activation and recently active CA1 cells during non-REM sleep.

    abstract::Sleep oscillations in the neocortex and hippocampus are critical for the integration of new memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood. To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; sl...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.48881

    authors: Varela C,Wilson MA

    更新日期:2020-06-11 00:00:00

  • Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning.

    abstract::Vertebrate embryonic patterning depends on signaling from Nodal, a TGFβ superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFβ member Vg1 is implicated in mesoderm formation but the role of the ze...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.28635

    authors: Pelliccia JL,Jindal GA,Burdine RD

    更新日期:2017-11-15 00:00:00

  • G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases.

    abstract::Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selec...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.04871

    authors: Chen R,Rato C,Yan Y,Crespillo-Casado A,Clarke HJ,Harding HP,Marciniak SJ,Read RJ,Ron D

    更新日期:2015-03-16 00:00:00

  • Selections that isolate recombinant mitochondrial genomes in animals.

    abstract::Homologous recombination is widespread and catalyzes evolution. Nonetheless, its existence in animal mitochondrial DNA is questioned. We designed selections for recombination between co-resident mitochondrial genomes in various heteroplasmic Drosophila lines. In four experimental settings, recombinant genomes became t...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.07247

    authors: Ma H,O'Farrell PH

    更新日期:2015-08-03 00:00:00

  • The connectome of the adult Drosophila mushroom body provides insights into function.

    abstract::Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome,...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.62576

    authors: Li F,Lindsey JW,Marin EC,Otto N,Dreher M,Dempsey G,Stark I,Bates AS,Pleijzier MW,Schlegel P,Nern A,Takemura SY,Eckstein N,Yang T,Francis A,Braun A,Parekh R,Costa M,Scheffer LK,Aso Y,Jefferis GS,Abbott LF,Litwi

    更新日期:2020-12-14 00:00:00

  • JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis.

    abstract::Exhaustion of stem cells is a hallmark of aging. In the Drosophila testis, dedifferentiated germline stem cells (GSCs) derived from spermatogonia increase during lifespan, leading to the model that dedifferentiation counteracts the decline of GSCs in aged males. To test this, we blocked dedifferentiation by mis-expres...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.36095

    authors: Herrera SC,Bach EA

    更新日期:2018-07-09 00:00:00

  • Runx2-Twist1 interaction coordinates cranial neural crest guidance of soft palate myogenesis.

    abstract::Cranial neural crest (CNC) cells give rise to bone, cartilage, tendons, and ligaments of the vertebrate craniofacial musculoskeletal complex, as well as regulate mesoderm-derived craniofacial muscle development through cell-cell interactions. Using the mouse soft palate as a model, we performed an unbiased single-cell...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.62387

    authors: Han X,Feng J,Guo T,Loh YE,Yuan Y,Ho TV,Cho CK,Li J,Jing J,Janeckova E,He J,Pei F,Bi J,Song B,Chai Y

    更新日期:2021-01-22 00:00:00

  • An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK.

    abstract::A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.14048

    authors: Hao Y,Frey E,Yoon C,Wong H,Nestorovski D,Holzman LB,Giger RJ,DiAntonio A,Collins C

    更新日期:2016-06-07 00:00:00

  • New insights into the mechanism of dynein motor regulation by lissencephaly-1.

    abstract::Lissencephaly ('smooth brain') is a severe brain disease associated with numerous symptoms, including cognitive impairment, and shortened lifespan. The main causative gene of this disease - lissencephaly-1 (LIS1) - has been a focus of intense scrutiny since its first identification almost 30 years ago. LIS1 is a criti...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.59737

    authors: Markus SM,Marzo MG,McKenney RJ

    更新日期:2020-07-21 00:00:00

  • Shared behavioral mechanisms underlie C. elegans aggregation and swarming.

    abstract::In complex biological systems, simple individual-level behavioral rules can give rise to emergent group-level behavior. While collective behavior has been well studied in cells and larger organisms, the mesoscopic scale is less understood, as it is unclear which sensory inputs and physical processes matter a priori. H...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.43318

    authors: Ding SS,Schumacher LJ,Javer AE,Endres RG,Brown AE

    更新日期:2019-04-25 00:00:00

  • Generalization of learned responses in the mormyrid electrosensory lobe.

    abstract::Appropriate generalization of learned responses to new situations is vital for adaptive behavior. We provide a circuit-level account of generalization in the electrosensory lobe (ELL) of weakly electric mormyrid fish. Much is already known in this system about a form of learning in which motor corollary discharge sign...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.44032

    authors: Dempsey C,Abbott LF,Sawtell NB

    更新日期:2019-03-14 00:00:00

  • Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2.

    abstract::During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripoten...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.21526

    authors: Scerbo P,Marchal L,Kodjabachian L

    更新日期:2017-06-27 00:00:00

  • SARS-CoV-2 (COVID-19) by the numbers.

    abstract::The COVID-19 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this article we provide a one-stop, curated graphical source for the key numbers (based mostly on the peer-reviewed literature) abou...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.57309

    authors: Bar-On YM,Flamholz A,Phillips R,Milo R

    更新日期:2020-04-02 00:00:00

  • Notochord vacuoles absorb compressive bone growth during zebrafish spine formation.

    abstract::The vertebral column or spine assembles around the notochord rod which contains a core made of large vacuolated cells. Each vacuolated cell possesses a single fluid-filled vacuole, and loss or fragmentation of these vacuoles in zebrafish leads to spine kinking. Here, we identified a mutation in the kinase gene dstyk tha...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.51221

    authors: Bagwell J,Norman J,Ellis K,Peskin B,Hwang J,Ge X,Nguyen SV,McMenamin SK,Stainier DY,Bagnat M

    更新日期:2020-01-29 00:00:00

  • Gene autoregulation by 3' UTR-derived bacterial small RNAs.

    abstract::Negative feedback regulation, that is the ability of a gene to repress its own synthesis, is the most abundant regulatory motif known to biology. Frequently reported for transcriptional regulators, negative feedback control relies on binding of a transcription factor to its own promoter. Here, we report a novel mechan...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.58836

    authors: Hoyos M,Huber M,Förstner KU,Papenfort K

    更新日期:2020-08-03 00:00:00

  • Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage.

    abstract::Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.12256

    authors: Lee SH,Princz LN,Klügel MF,Habermann B,Pfander B,Biertümpfel C

    更新日期:2015-12-18 00:00:00

  • The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism.

    abstract::Ki-67 and RepoMan have key roles during mitotic exit. Previously, we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan (Booth et al., 2014). Here we show how Ki-67 and RepoMan form mitotic exit phosphatas...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.16539

    authors: Kumar GS,Gokhan E,De Munter S,Bollen M,Vagnarelli P,Peti W,Page R

    更新日期:2016-08-30 00:00:00

  • An unfolded protein-induced conformational switch activates mammalian IRE1.

    abstract::The unfolded protein response (UPR) adjusts the cell's protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.30700

    authors: Karagöz GE,Acosta-Alvear D,Nguyen HT,Lee CP,Chu F,Walter P

    更新日期:2017-10-03 00:00:00

  • Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1.

    abstract::Cardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a CTG repeat disorder involving misbalance between two RNA binding factors, MBNL1 and CELF1. However, how DM1 condition translates into conduction disorders remains poorly understood. Here we simulated MBNL1 and CELF1 misbalance in...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.51114

    authors: Auxerre-Plantié E,Nakamori M,Renaud Y,Huguet A,Choquet C,Dondi C,Miquerol L,Takahashi MP,Gourdon G,Junion G,Jagla T,Zmojdzian M,Jagla K

    更新日期:2019-12-12 00:00:00

  • Dissection of specific binding of HIV-1 Gag to the 'packaging signal' in viral RNA.

    abstract::Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis-acting RNA element called the 'packaging signal' (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.27055

    authors: Comas-Garcia M,Datta SA,Baker L,Varma R,Gudla PR,Rein A

    更新日期:2017-07-20 00:00:00

  • Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.

    abstract::Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, c...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.31515

    authors: Burkhard SB,Bakkers J

    更新日期:2018-02-05 00:00:00